Variables affecting penetrance of gastric and duodenal phenotype in familial adenomatous polyposis patients

Danielle C Sample, N Jewel Samadder, Lisa M Pappas, Kenneth M Boucher, Wade S Samowitz, Therese Berry, Michelle Westover, Deepika Nathan, Priyanka Kanth, Kathryn R Byrne, Randall W Burt, Deborah W Neklason, Danielle C Sample, N Jewel Samadder, Lisa M Pappas, Kenneth M Boucher, Wade S Samowitz, Therese Berry, Michelle Westover, Deepika Nathan, Priyanka Kanth, Kathryn R Byrne, Randall W Burt, Deborah W Neklason

Abstract

Background: Patients with familial adenomatous polyposis (FAP) frequently undergo colectomy to reduce the 70 to 90% lifetime risk of colorectal cancer. After risk-reducing colectomy, duodenal cancer and complications from duodenal surgeries are the main cause of morbidity. Our objective was to prospectively describe the duodenal and gastric polyp phenotype in a cohort of 150 FAP patients undergoing pre-screening for a chemoprevention trial and analyze variables that may affect recommendations for surveillance.

Methods: Individuals with a diagnosis of FAP underwent prospective esophagogastroduodenoscopy using a uniform system of mapping of size and number of duodenal polyps for a 10 cm segment. Gastric polyps were recorded as the total number.

Results: The distribution of the count and sum diameter of duodenal polyps were statistically different in two genotype groups, those with APC mutations associated with classic FAP had a greater count (median 17) and sum diameter of polyps (median 32 mm) than those with APC mutations associated with attenuated FAP (median count 4 and median sum diameter of 7 mm) (p < 0.0001). The number of gastric polyps did not differ based on genotype (p = 0.67) but advancing age correlated with severity of gastric polyposis (p = 0.019). Spigelman (modified) staging of II or greater was found in 88% of classic FAP patients and 48% attenuated FAP patients. Examples of severe and mild upper GI phenotype are observed in patients with identical APC mutations, showing that the APC mutation location is not absolutely predictive of an upper GI phenotype.

Conclusions: Most FAP patients have duodenal and gastric polyps which become more prevalent and advanced with age. Standard upper endoscopic surveillance is recommended based on personal history independent of APC mutation location.

Trial registration: NCT 01187901 registered August 24, 2010, prospective to enrollment.

Trial registration: ClinicalTrials.gov NCT01187901.

Keywords: Duodenum; Familial adenomatous polyposis; Fundic gland polyps; Gastric; Polyposis.

Conflict of interest statement

Ethics approval and consent to participate

All aspects of this study were approved by University of Utah’s Institutional Review Board for human subject research. All patients participating gave written informed consent and authorization for use of data.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Sum diameter of duodenal polyps grouped by age at colectomy. The study consisted of 110 subjects with a colectomy and divided into 4 age groups and one group that had not had colectomy (25 juvenile at age 8–17 years indicated by (○); 38 young adult at age 18–30 years indicated by (Δ); 29 adult at age 31–40 years indicated by (+) and 18 mature adult at age 41 or older indicated by (x)) and 40 who had not undergone a colectomy at time of upper endoscopy (NA) indicated by (◊). Each individual is plotted based on duodenal polyp burden in millimeters versus the age when the duodenal data were captured by endoscopy
Fig. 2
Fig. 2
Modified Spigelman stage and gastric polyp number relative to APC mutation location Patients were divided into 5 groups based on the location of the APC mutation: Attenuated polyposis (n = 71), patients with mutations consistent with attenuated FAP (5′ to c.532, exon 9 alternative splice site c.936-c.1236, intron 9 and 3′ to c. 4785). Intermediate polyposis (n = 42); Profuse polyposis (n = 17) patients with mutations consistent with profuse colonic polyposis (c.3750-c.4392); Deletion of multiple APC exons (n = 6) and deletion of promoter 1B (n = 5). Figure shows percent and number of patients in each APC mutation group by (Panel a) modified Spigelman stage of duodenal polyposis or (Panel b) gastric polyp number. Gastric polyps were estimated as described in methods and set at a maximum of 100

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